Transwomen bear a disproportionate burden of HIV worldwide, yet incidence is seldom measured and the determinants of acquiring infection are unknown. There is no HIV prevention intervention for transwomen with evidence of efficacy. Our project's goals are to create an international platform for HIV epidemiology and prevention research for transwomen, obtain benchmarks for HIV incidence, and characterize causal factors for infection. We propose a cohort study of 1,100 transwomen in San Francisco, USA and So Paulo, Brazil where capacities are ready for longitudinal research. The cohort will measure HIV incidence and test hypotheses on HIV acquisition related to social and biomedical gender transition events and components of the Gender Affirmation, Behavioral Ecological, and Minority Stress models. Meanwhile, little is known about transwomen in China, the world's largest country, or sub- Saharan Africa, where the HIV epidemic is most severe. Basic epidemiological research on transwomen in these regions is overdue. We therefore also propose a cross-sectional survey of 250 transwomen in Nanjing, China and a formative assessment of transwomen in Windhoek, Namibia. In addition to obtaining the first estimates of HIV prevalence among transwomen in China and the first focused study of transwomen in sub-Saharan Africa, we will prepare these sites for future inclusion in the cohort. Our specific aims for the current proposal are: 1) to establish a population-based cohort of transwomen in San Francisco and So Paulo to measure HIV incidence; 2) to test hypotheses on social and biomedical gender transition events as causal factors in HIV acquisition among transwomen; 3) to initiate HIV prevention research for transwomen in China and sub-Saharan Africa. We will use respondent-driven sampling (RDS) for recruitment in order to approximate population-based samples for high external validity. Social media and mobile and web-based technologies will be used to increase cohort retention for high internal validity. HIV is only one health disparity experienced by transwomen. Transwomen are at increased risk for multiple mental health disorders and little is known about the impact of gender transition procedures on non-communicable diseases. The project will culminate in an international collaborative for rigorous HIV prevention research with incident endpoints and an infrastructure for ancillary studies on transwomen health issues.